Treatment of Clostridioides difficile infection (CDI) in adults

Treatment of Clostridioides difficile infection (CDI) in adults

Clinical condition	Treatment
Nonfulminant disease
Initial episode (nonsevere or severe disease)	Management of an initial CDI episode consists of treatment with an antibiotic regimen.
Nonsevere disease is supported by the following clinical data: White blood cell count ≤15,000 cells/mL and serum creatinine level <1.5 mg/dL Severe disease* is supported by the following clinical data: White blood cell count >15,000 cells/mL and/or serum creatinine level ≥1.5 mg/dL	Antibiotic regimens: Fidaxomicin^¶ 200 mg orally twice daily for 10 days Vancomycin^Δ 125 mg orally 4 times daily for 10 days For nonsevere disease, alternative regimen if above agents are unavailable: Metronidazole^◊ 500 mg orally 3 times daily for 10 to 14 days
Recurrent episode^§	Management of a recurrent CDI episode consists of treatment with an antibiotic regimen, in addition to adjunctive bezlotoxumab^¶ if feasible.
First recurrence	Antibiotic regimens: Fidaxomicin^¶ 200 mg orally twice daily for 10 days, OR 200 mg orally twice daily for 5 days, followed by once every other day for 20 days Vancomycin^Δ in a tapered and pulsed regimen, for example: 125 mg orally 4 times daily for 10 to 14 days, then 125 mg orally 2 times daily for 7 days, then 125 mg orally once daily for 7 days, then 125 mg orally every 2 to 3 days for 2 to 8 weeks Vancomycin^Δ 125 mg orally 4 times daily for 10 days Adjunctive treatment: Bezlotoxumab^¶^¥ 10 mg/kg intravenously, given once during administration of standard antibiotic regimen.
Second or subsequent recurrence	Antibiotic regimens: Fidaxomicin^¶ 200 mg orally twice daily for 10 days, OR 200 mg orally twice daily for 5 days, followed by once every other day for 20 days Vancomycin^Δ in a tapered and pulsed regimen (example as above) Vancomycin^Δ followed by rifaximin: Vancomycin 125 mg orally 4 times daily by mouth for 10 days, then Rifaximin 400 mg orally 3 times daily for 20 days Adjunctive treatment: Bezlotoxumab^¶^¥ 10 mg/kg intravenously, given once during administration of standard antibiotic regimen. Role of fecal microbiota transplantation (FMT): For patients who have received appropriate antibiotic treatment for at least 3 CDI episodes (ie, initial episode plus 2 recurrences), who subsequently present with a fourth or further CDI episode (third or subsequent recurrence), we favor FMT in regions where available^‡. Pending referral for FMT, we treat with an antibiotic regimen as outlined above.
Fulminant disease
Fulminant disease* is supported by the following clinical data: Hypotension or shock, ileus, megacolon	Absence of ileus: Enteric vancomycin plus parenteral metronidazole^†: Vancomycin^Δ 500 mg orally or via nasogastric tube 4 times daily, AND Metronidazole 500 mg intravenously every 8 hours If ileus is present, additional considerations include: FMT (administered rectally)** OR Rectal vancomycin (administered as a retention enema 500 mg in 100 mL normal saline per rectum; retained for as long as possible and readministered every 6 hours)^¶¶

The standard course of treatment for an initial episode of CDI is 10 days. Some patients, particularly those treated with metronidazole or with severe disease, may have a delayed response; in such circumstances, treatment may be extended to 14 days. For patients with inflammatory bowel disease, an extended duration of 14 days is also appropriate. If continuation of antibiotic(s) for a primary infection is essential, we continue CDI treatment for one week after completion of other antibiotics.

* The criteria proposed for defining severe or fulminant CDI are based on expert opinion and may need to be reviewed upon publication of prospectively validated severity scores for patients with CDI. Patients with severe or fulminant CDI also warrant assessment for surgical indications; refer to UpToDate topic on treatment of CDI for further discussion.

¶ For patients with nonfulminant disease, we suggest a fidaxomicin-based regimen over a vancomycin-based regimen. In addition, for patients with nonfulminant recurrent disease and prior CDI in the last 6 months, we suggest adjunctive bezlotoxumab. Use of fidaxomicin or bezlotoxumab have each been associated with a small benefit with respect to CDI recurrence rates (10 to 15% decrease). In the setting of cost constraints, we prioritize use of these agents for patients at greatest risk for CDI recurrence (age ≥65 years, severe CDI, or immunosuppression). Vancomycin remains an acceptable agent for treatment of initial and recurrent CDI.

Δ Systemic absorption of enteral vancomycin can occur in patients with mucosal disruption due to severe or fulminant colitis; this consideration is particularly important for patients with kidney insufficiency (creatinine clearance <10 mL/minute). Therefore, monitoring serum vancomycin levels is warranted for patients with kidney failure who have severe or fulminant colitis and require a prolonged course (>10 days) of enteral vancomycin therapy.

◊ Metronidazole should be avoided in patients who are frail, age >65 years, or who develop CDI in association with inflammatory bowel disease. Caution is also warranted during pregnancy and lactation.

§ The approach to antibiotic management of nonfulminant recurrent CDI is the same regardless of severity, but varies depending on the number of recurrences, as outlined above. For patients with a recurrent episode of CDI that is severe, refer to UpToDate topic on treatment of CDI for further discussion.

¥ The bezlotoxumab prescribing information in the United States warns that in patients with a history of congestive heart failure, the drug should be reserved for use when the benefit outweighs the risk, given reports of increased heart failure exacerbations and associated deaths in such patients. In addition, data for use of bezlotoxumab combined with fidaxomicin are limited.

‡ In contrast to the above approach, some favor FMT for patients who have received antibiotic treatment for at least 2 CDI episodes (ie, initial episode plus one recurrence), who subsequently present with a third or further CDI episode (second or subsequent recurrence)^[1].

† Continue dosing for 10 days. If recovery is delayed, treatment can be extended to 14 days.

** In the setting of ileus, we favor FMT over rectal vancomycin. However, such procedures are associated with risk of colonic perforation; therefore, they should be restricted to patients who are not responsive to standard therapy, and the procedure should be performed by personnel with appropriate expertise. Refer to the UpToDate topic on FMT for discussion of safety, efficacy, and delivery protocols.

¶¶ Rectal vancomycin may be administered as a retention enema, either in addition to oral vancomycin (if the ileus is partial) or in place of oral vancomycin (if the ileus is complete). Given potential risk of colonic perforation in setting of CDI, rectal vancomycin instillation should be performed by personnel with appropriate expertise.

Adapted from: Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis 2021; 24:ciab549. By permission of Oxford University Press on behalf of IDSA and SHEA. Copyright © 2021. Available at: https://www.idsociety.org/practice-guideline/clostridioides-difficile-2021-focused-update/. OUP and the IDSA are not responsible or in any way liable for the accuracy of the adaptation. The Licensee is solely responsible for the adaptation in this publication.

Reference:

Kelly CR, Fischer M, Allegretti JR, et al. ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections. Am J Gastroenterol 2021; 116:1124.

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Treatment of Clostridioides difficile infection (CDI) in adults